David Drew

Dr David Drew

Research Fellow

Organisation

Imperial College London

Research summary

A large portion of the food we consume is broken down into simple sugars, such as glucose and fructose that our body uses as fuel. For cells to convert sugar into energy, the sugars must be transported from the bloodstream and into the cells where this takes place. Specialised protein machines, so called ‘GLUT transporters’, are embedded into the cells membrane to carry out this task. How do these GLUT proteins shuttle sugar into the cell? Currently we hypothesize that GLUTs form a pore that is only accessible on one side of the membrane at a time. The entry of sugar probably acts like a switch to close the pore and open another on the opposite side, i.e., in this way the sugar is moved across the cell’s membrane. The best way to understand how this works is to use a technique called X-ray protein crystallography that enables us to capture the three-dimensional structure of this protein in action. Because this is very difficult, no one has been successfully determined the shape of this protein nor any others like it. Indeed, despite the tremendous painstaking effort of many research groups for more than 20 years, only a handful of human structures are known. As more than 40% of small molecule drug targets are aimed at membrane proteins, each 3D-structure is eagerly anticipated by both academia and the pharmaceutical industry. Similarly, because GLUT proteins are involved in many diseases, e.g., such as breast cancer, they are an attractive area for design of better medicines. Simplistically, breast tumours need more energy than normal cells to grow and use the sugar fructose to do this. With a 3D-structure it opens up the possibility to develop a therapeutic that will plug up the protein and stop it working, and in doing so, starve the cancerous cells of the fuel needed to grow.